Freezing bags

ABSTRACT

A freezing bag (10) for the storage of blood cells is formed from two sheets (11) of material joined together with welds (15, 18) defining a containment zone (19). A pocket (20) leads from the containment area (19) and in the weld (18) defining this pocket is an access port (17). An access tube (23) is secured to the port (17) and normally lies within the bounds of a pouch (21) formed by extensions of the sheets (11) beyond the containment zone (19).

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to bags for use in the preservation ofblood cells.

2. Discussion of Prior Art

Blood used for transfusion is normally stored in refrigerators, at atemperature of 4°±2°, where its safe life is no longer than six weeks.Potentially longer storage life might be obtained by freezing, butunfortunately freezing blood as obtained from a donor results indestruction of the red blood cells making the blood totally unsuitablefor transfusion. Red blood cells can be stored after separation fromother blood components, by centrifuging, plasma, mixing with acryoprotectant, and then freezing. The usual cryoprotectant is glycerol.As glycerol itself is poisonous frozen cells must have all the glycerolremoved therefrom before being used for transfusion. The necessaryremoval process, involving centrifugation and multiple washing steps, isa skilled and time-consuming task which also results in a significantloss of viable blood cells.

Another cryoprotectant is hydroxyethyl starch (HES), which is a widelyused artificial plasma expander and is non-toxic. Much work has beencarried out on methods of preserving red blood cells using thissubstance. Early efforts were unsuccessful, as it was found that thelevel of haemolysis (breakdown of red blood cells) in units of blood (aunit of blood being the volume of a standard donation, about 450 ml)recovered after freezing was above the safe limit. It is usuallyconsidered that a unit of blood is safe for transfusion if the level ofhaemolysis at thaw is no greater than 1%. A method of preserving andrecovering red blood corpuscules by freezing, using HES as acryoprotectant, wherein the level of haemolysis after recovery is withinacceptable limits, has now been developed and is described in PatentApplication PCT/GB90/0140.

The bags used in the method of PCT/GB90/0140 must be capable offulfilling stringent criteria. Freezing is carried out in liquidnitrogen, and is accompanied by unavoidable changes in volume of themixture of red blood cells and cryoprotectant. As explained inPCT/GB90/0140 the manner in which this change of volume is accommodatedby control of the thickness of the freezing bag during freezing iscritical. It is also important that the concentration of HES is withinstringent limits, and that the process of transferring donated blood tothe freezing bag is carried out in a sterile manner.

It has been suggested that the HES be stored in the freezing bag itself.However it has been found that the materials suitable for manufacturingthe bag are slightly porous, allowing the concentration of HES thereinto vary, the nature of the variation being dependant on the atmospherichumidity of the storage area.

It is also important that the bags, which must, once filled with blood,be stored at sub-zero temperatures of, for example -100°, should be of aconvenient shape for storage. It must also be possible to allow theblood, after thawing to flow from the bag in a sterile manner fortransfusion purposes. Bags which fulfil these criteria are described inPatent Applications WO 89/04280 and WO 91/11968. The manner ofextraction from these involves penetration by a needle of a special portbuilt into the bag. This procedure requires skill, presents the blood ina format not usually recognised by nursing staff, and also breaches theabsolute microbiological integrity of the bag. A fluid storage baghaving a single port, described as an outlet port, is illustrated inU.S. Pat. No. 4,256,333. The port is formed from a tube attached to thebag and a closure, and the disclosure is concerned with details of thejoint between the tube and the closure.

SUMMARY OF THE INVENTION

According to the present invention, a freezing bag includes two sheetsof material joined together by a weld to define a containment zonehaving a bottom edge, two side edges and an access edge, characterisedin that there is a single access port in the access edge and in that thesheets of material extend beyond the limits of the containment zone toform an open pouch, the pouch being defined by the access edge of thecontainment zone, extensions of the weld forming the side edges of thecontainment zone, and ends of the sheets.

The port is preferably situated in a pocket defined in part by at leastpart of the access edge and which leads into the containment zone.

A tube is positioned on the port, and may be secured thereto, by, forexample, a small metal collar. The tube may be pre-formed to lie withinthe bounds of the pouch.

The port is preferably formed integrally with an insert which ispositioned in the access edge of the bag prior to welding of that edge.

The pocket in the access edge of the bag may be formed by angling ofthat edge at other than a right angle to the side edges.

A fluid storage container having pouches is described in U.S. Pat. No.3,520,471, in which two fluid collecting conduits are positioned in apouch at one end of the container and a fluid dispensing conduit ispositioned in a pouch at an opposite end of the container.

According to another aspect of the present invention a method offreezing red blood cells includes;

taking a freezing bag, the bag being formed from two sheets of materialwelded together to form a containment zone having a bottom edge, twoside edges and an access edge, at least part of the access edge definingpart of a pocket which leads into the containment zone, that part of theaccess edge having therein an insert having a port to which is attacheda tube, the tube lying within an open pouch formed by extensions of thesheets beyond the extent of the bag;

sterile docking the tube to a supply of centrifuged red blood cells andtransferring the red blood cells to the bag;

disconnecting the supply of red blood cells, sterile docking the tube toa supply of HES, and transferring the HES to the bag;

manipulating the bag to expel, as far as is practical, all airtherefrom;

sealing the tube and then breaking the docking to the HES supply;

agitating the contents of the bag to thoroughly mix the blood cells andthe HES; and

placing the bag in a freezing frame and freezing the contents byimmersing the frame and bag in liquid nitrogen.

The tube adjacent the port may be clipped during the freezing process.

Before immersing the bag in liquid nitrogen the pouch may be treated.For example by rollers or in a press, to expel air therefrom, and itsopen end sealed, the arrangement being such that the tube is completelycontained within the sealed pouch.

The relative proportions of red blood cells, freezing methods, andmethods of recovery of the frozen cells in a form suitable fortransfusion, along with other details of the process, are fullydescribed elsewhere, for example in WO 90/09184, and will not be furtherdescribed here.

Once the blood has been prepared for transfusion the sealed pouch can bebreached and the tube connected to standard transfusion apparatus in theconventional manner.

In order to fulfil the requirements of PCT/GB90/140 the containment zonepreferably has an area of approximately 0.102 square meters, and theweld, at least at the corners between the side edges and the bottomedges, is radiussed.

BRIEF DESCRIPTION OF THE DRAWINGS

Some embodiments of the invention will now be described, by way ofexample only, with reference to the accompanying diagrammatic drawings,of which:

FIG. 1 is a plan view of a freezing bag according to the invention.

FIG. 2 is a detail of part of the freezing bag shown in FIG. 1,

FIGS. 3A₁, 3A₂, B, C and D are a perspective views of four alternativeversions of insert as shown in FIG. 2,

FIG. 4 is a plan view of the bag in use, and

FIGS. 5 and 6 and 7 are plan views of alternative designs of the bagshown in FIG. 1.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

A freezing bag 10 (FIG. 1) is formed from two sheets of material, showngenerally at 11. A bottom edge 12 and side edges 13, 14 of the sheetsare joined together by a first weld 15. An insert 16 having an integralport 17 is positioned towards the top of and between the sheets 11 andthe sheets 11 are joined together by a second weld 18 which is angledupwardly (relative to a right angle) from the weld 15 at one side 14 ofthe sheets 11, and which defines an access edge, overlies the insert 16such that there is a passage across the weld 18, then curves downwardlyto meet the weld 15 at the side 14 of the sheets 11. The welds 15, 18thus define a containment zone 19 which is sealed other than through theinsert 16 and port 17, and the insert 16 is positioned towards the topof a pocket 20 defined by the normal to the weld 15 at its junction withthe weld 18 and the weld 18.

An open pouch 21 is defined by the extent of the sheets 11 beyond thecontainment zone 19 and pocket 20, the pouch being defined by the weld18, extensions of the weld 15, and ends 22 of the sheets 11. A tube 23(not shown in FIG. 1, but see FIG. 2) is attached to the port 17 and issecured thereto by a metal collar 24.

Suitable shapes of insert 16 are illustrated in FIG. 3.

In use (FIG. 4) the bag 10 is removed from store and the tube 23 issterilely docked to a supply tube 25 which leads from a blood bag 26containing red blood cells (which may be buffy coat depleted), obtainedfrom a standard unit blood donation by means, such as centrifuging,etc., well known in the art, and the blood cells are transferred to thecontainment zone 19. The supply tube 25 is then disconnected and a tube27, leading from a HES supply 28, is connected to the tube 23 by steriledocking. HES is passed to the containment zone 19 and the bag ismanipulated to expel, as far as is practical, all air from thecontainment zone 19. The tube 23 is then sealed and the tubes 23, 27separated. The bag 10 is then manipulated to thoroughly mix the redblood cells and HES.

After mixing, a clip 29 (FIG. 2) is used to close the tube 23 adjacentthe port 17, the tube 23 is positioned within the pouch 21, air isexpelled from the pouch 21 (by, example, use of a press) and top edges22 of the sheets 11 are welded together to seal the pouch 21. The bag isthen positioned in a freezing frame (a procedure well known in the art,and hence not described here) which is placed in known fashion in liquidnitrogen to freeze the mixture. The clip 29 is helps to prevent bloodcells from being drawn from the containment area 19 into the tube 23during the freezing process. Whilst it is not necessary to evacuate andseal the pouch 21 doing so prevents liquid nitrogen from directlyaccessing the area of the insert 16 and port 17 so ensuring thatnitrogen cannot enter the containment area even if there is a weaknessin the juncture of the insert 16 and weld 18.

Once the mixture has been frozen the bag is stored according to themethod of PCT/GB/90/0140.

In order to meet the stringent requirements of the method ofPCT/GB90/0140 (i.e. controlling an optimum thickness of contents whenfreezing a standard unit of blood) the containment zone has an area ofapproximately 0.102 sq. meters, and the welds 15, 18 at the corners ofthe containment zone 19 are curved. The containment zone 19, apart fromthe pocket 20, is advantageously rectangular, almost square, in shape,and suitable approximate dimensions are similar to those shown in FIG.1, namely an overall bag length of 395 mm and width of 325 mm, withlengths between weld 18 and weld 15 at the bottom edge 12, at ends ofthe pocket 20, being respectively 340 and 300 mm with welds 15 18 4 mmwide, weld 15 being inset 6 mm from edges 14, 13 of sheets 11 andcorners having radii of 46 mm. At the corners of the bottom edge 12,external to the containment zone 19, are two reinforced hangingapertures 30.

When the stored blood is required it is thawed according to the methodof PCT/GB/90/0140 and the tube 23 connected by a sterile docking deviceto any regular transfusion bag. The thawing process, which is extremelysimple, is the only task not familiar to those used to giving bloodtransfusions and the blood for transfusion is presented to medical andnursing staff in a bag with which they are familiar.

As the absolute microbiological integrity of the blood is notcompromised during donation, storage, thawing, or transfer from thefreezing bag 10;

a) the blood can be stored for a time in a normal blood bank afterthawing, if it is not required for transfusion immediately, b) anoptimal additive solution can be added to prolong the shelf life of theblood, c) a unit of blood can be washed, if this is thought to berequired, d) plasma, autologous or homologous, can be added to the redcells in a sterile manner, and e) after the blood has been removed fromthe freezing bag 10 it is possible to segmentalise the outlet tube 23 toallow numerous cross-matches to be performed with the blood remainingtherein.

This design of bag is easy to label in a manner which will preventtransfusion of an incorrect unit, to allow a unit to be traced back tothe donor, and otherwise. The label can be attached to one of the sheets11 in the area forming the pouch 21 as a donation is being transferredto the containment zone 19, minimising the danger of incorrectlabelling. A label in this area will not affect heat transfer from themixture during the freezing process.

Whilst the sheets 11 have been described as single layers it will berealised that each sheet might in fact be multi-layered.

Materials suitable for use with the invention are Kapton F and Teflon,although other suitable materials will be readily apparent to thoseskilled in the art. Many plastic materials have the required flexibilityand resistance to low temperatures. For example metallised plasticmaterial may be used. Depending on the material used, it may be possibleto form the bag 10 using a single welding process rather than using twowelds 15, 18 as described above.

It will also be realised that the dimensions and thicknesses quotedabove are examples only, and may be varied.

Other embodiments of bag are illustrated in FIGS. 5 to 7, and otherembodiments of the above described ideas, within the scope of theinvention, will also be readily apparent to those skilled in the art.

What is claimed is:
 1. A freezing bag comprising:two sheets of aweldable plastic material joined together by a weld defining acontainment zone having a bottom edge, two side edges and an access edgesaid sheets including ends, a single access port in the access edgewherein the ends of the sheets of material extend beyond the limits ofthe containment zone and comprise an open pouch, the pouch being definedby the access edge of the containment zone, extensions of the weldforming the side edges of the containment zone, and ends of the sheets.2. A freezing bag as claimed in claim 1 wherein the port is situated ina pocket defined in part by at least part of the access edge and whichleads into the containment zone.
 3. A freezing bag as claimed in claim 2wherein the pocket is formed by angling of the access edge at other thana right angle to the side edges.
 4. A freezing bag as claimed in claim 1wherein a tube is positioned on the port.
 5. A freezing bag as claimedin claim 6 wherein the tube is secured to the port.
 6. A freezing bag asclaimed in claim 7 wherein the tube is secured to the port by a metalcollar.
 7. A freezing bag as claimed in claim 1 wherein a tubepositioned on the port is preformed to lie within the bounds of thepouch.
 8. A freezing bag as claimed in claim 1 wherein the port isformed integrally with an insert which is positioned in the access edgeof the bag prior to welding of that edge.
 9. A freezing bag as claimedin claim 1 wherein the containment zone and pocket have an area ofapproximately 0.102 square meters.
 10. A freezing bag as claimed inclaim 1 wherein the weld, at the corners between the edges, isradiussed.
 11. A method of freezing red blood cells comprising the stepsof:providing a freezing bag, the bag being formed form two sheets ofweldable plastic material welded together to form a containment zonehaving a bottom edge, two side edges and an access edge, at least partof the access edge defining part of a pocket which leads into thecontainment zone, that part of the access edge having therein an inserthaving a port to which port is attached a tube, the tube lying within anopen pouch formed by extensions of the sheets beyond the extent of thecontainment zone; connecting the tube to a supply of centrifuged andbuffy-coat depleted red blood cells; transferring the red blood cells tothe bag; disconnecting the supply of red blood cells; sterile dockingthe tube to a supply of HES; transferring the HES to the bag;manipulating the bag to expel air therefrom; sealing the tube andsimultaneously breaking the docking to the HES supply; agitating thecontents of the bag to thoroughly mix the blood cells and the HES; andplacing the bag in a freezing frame and freezing the contents byimmersing the frame and bag in liquid nitrogen.
 12. A method of freezingred blood cells as claimed in claim 11 wherein, before immersing the bagin liquid nitrogen, the pouch is treated to expel air therefrom and itsopen end sealed with the tube completely contained within the sealedpouch.
 13. A method of freezing red blood cells as claimed in claim 11wherein the tube adjacent the port is clipped during the freezingprocess.
 14. A freezing bag comprising:two sheets of bondable plasticmaterial joined together by a bonded peripheral seal, the seal beingmade to define a containment zone between the sheets, the containmentzone having a bottom edge, two side edges and an access edge; a pocketleading into the containment zone and formed from part of the accessedge; a single access port positioned in a part of the access edgeforming the pocket; a tube secured to the access port; and an open pouchformed from extensions of sheets beyond the containment zone and pocket,the pouch being defined by the access edge and extensions of the sealforming the side edges beyond the access edge and the ends of the sheetsso as to provide a sealable closure for retaining the tube thereinduring freezing.
 15. A freezing bag as claimed in claim 14 wherein thepocket is formed by angling of the access edge at other than a rightangle to the side edges.
 16. A freezing bag as claimed in claim 14wherein the tube is secured to the port by a metal collar.
 17. Afreezing bag as claimed in claim 14 wherein the tube is preformed to liewithin the bounds of the pouch.
 18. A freezing bag as claimed in claim14 wherein the seal at the corners between the edges is radiussed.
 19. Afreezing bag as claimed in claim 14 wherein the port is formedintegrally with an insert which is positioned in the access edge priorto bonding of that edge.
 20. A method of freezing red blood cellscomprising the steps of:providing a freezing bag as claimed in claim 14;connecting the tube to a supply of centrifuged and buffy-coat depletedred blood cells and transferring the red blood cells to the bag;disconnecting the supply of red blood cells, sterile docking the tube toa supply of hydroxyethyl starch (HES) and transferring the HES to thebag; manipulating the bag to expel air therefrom; sealing the tube andsimultaneously breaking the docking to the HES supply; agitating thecontents of the bag to thoroughly mix the blood cells and the HES;treating the pouch to expel air therefrom and sealing the pouch tocompletely contain the tube therein; and placing the sealed bag in afreezing frame and freezing the contents by immersing the frame inliquid nitrogen.
 21. A method of freezing red blood cells as claimed inclaim 20, wherein the tube adjacent the port is clipped during thefreezing process.